The pentose phosphate pathway has two metabolic functions: (1) generation of nicotinamide adenine dinucleotide phosphate (reduced
NADPH), for reductive biosynthesis, and (2) formation of
ribose, which is an essential component of
ATP,
DNA, and
RNA. Transaldolase links the pentose phosphate pathway to
glycolysis. In patients with deficiency of transaldolase, there's an accumulation of
erythritol (from
erythrose 4-phosphate), D-
arabitol, and
ribitol.[5][6]
The deletion in 3 base pairs in the TALDO1 gene results in the absence of serine at position 171 of the transaldolase protein, which is part of a highly conserved region, suggesting that the mutation causes the transaldolase deficiency that is found in
erythrocytes and
lymphoblasts.[5] The deletion of this amino acid can lead to
liver cirrhosis and
hepatosplenomegaly (enlarged spleen and liver) during early infancy. Transaldolase is also a target of
autoimmunity in patients with
multiple sclerosis.[7]
Structure
Active site of the transaldolase enzyme highlighting the key amino acid residues (Asp-27, Glu-106, and Lys-142) involved in catalysis.[1]
Transaldolase is a single domain composed of 337 amino acids. The core structure is an
α/β barrel, similar to other class I aldolases, made up of eight parallel
β-sheets and seven
α-helices. There are also seven additional α-helices that are not part of the barrel. Hydrophobic amino acids are located between the β-sheets in the barrel and the surrounding α-helices to contribute to packing, such as the area containing Leu-168, Phe-170, Phe-189, Gly-311, and Phe-315. In the crystal, human transaldolase forms a dimer, with the two subunits connected by 18 residues in each subunit. See mechanism to the left for details.
The active site, located in the center of the barrel, contains three key residues: lysine-142, glutamate-106, and aspartate-27. The lysine holds the sugar in place while the glutamate and aspartate act as proton donors and acceptors.[1]
Mechanism of catalysis
The residue of lysine-142 in the active site of transaldolase forms a
Schiff base with the keto group in
sedoheptulose-7-phosphate after deprotonation by another active site residue, glutamate-106. The reaction mechanism is similar to the reverse reaction catalyzed by
aldolase: The bond joining carbons 3 and 4 is broken, leaving
dihydroxyacetone joined to the enzyme via a Schiff base. This cleavage reaction generates the unusual aldose sugar
erythrose-4-phosphate. Then transaldolase catalyzes the condensation of
glyceraldehyde-3-phosphate with the Schiff base of
dihydroxyacetone, yielding enzyme-bound
fructose 6-phosphate. Hydrolysis of the Schiff base liberates free
fructose 6-phosphate, one of the products of the pentose phosphate pathway.
Reaction scheme for the conversion of sedoheptulose-7-phosphate to fructose-6-phosphate.[8]
The pentose phosphate pathway adapted from (Verhoeven, 2001)[5]
^Molecular graphics images were produced using the UCSF Chimera package from the Resource for Biocomputing, Visualization, and Informatics at the University of California, San Francisco. Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, Meng EC, Ferrin TE (October 2004). "UCSF Chimera–a visualization system for exploratory research and analysis". J Comput Chem. 25 (13): 1605–12.
CiteSeerX10.1.1.456.9442.
doi:
10.1002/jcc.20084.
PMID15264254.
S2CID8747218.
^Banki K, Eddy RL, Shows TB, Halladay DL, Bullrich F, Croce CM, Jurecic V, Baldini A, Perl A (October 1997). "The human transaldolase gene (TALDO1) is located on chromosome 11 at p15.4-p15.5". Genomics. 45 (1): 233–8.
doi:
10.1006/geno.1997.4932.
PMID9339383.
![Reaction scheme for the conversion of sedoheptulose-7-phosphate to fructose-6-phosphate.[8]](/info/en/?search=File:Transaldolasemech.jpg)
![The pentose phosphate pathway adapted from (Verhoeven, 2001)[5]](/info/en/?search=File:Transaldolaserepofppp.jpg)
